Procedures for the treatment of cancer generally have been based upon the natural history of tumor spread, and thence, upon operative and non-operative options available to the physician. Operative options generally have looked to the physical identification and surgical resection of tumor(s). A variety of techniques have been brought to bear in the art with the purpose of aiding the surgeon in detecting and localizing neoplastic tissue as part of this surgical procedure. (“Neoplastic tissue,” for the present purposes, often is referred to as cancerous tissue, though malignant tumor and malignant tumor cells also are found in the terminology of the art. The term “neoplastic tissue” includes all of these.) Typically, large tumor(s) are readily located by the surgeon by visualization at the operating theater, and, in particular, through palpation, i.e., the feel of a tumor as opposed to that of normal tissue. To achieve operative success, however, it is necessary for the surgeon to somehow locate “occult” tumor(s), i.e., tumor(s) that cannot be located by the conventional surgical procedures of sight and feel. Failure to locate and remove such occult tumor(s) generally will result in the continued growth of cancer in the patient, a condition often referred to as “recurrent” cancer.
A much improved method for locating, differentiating, and removing neoplasms uses a radiolabeled antibody injected into the patient. Once injected, such antibodies are known to accumulate in neoplastic tissues at a higher concentration than in normal tissue. A portable radiation detection probe is employed by a surgeon intraoperatively in order to detect sites of radioactivity. Because of the proximity of the detection probe to the labeled antibody, the faint radiation emanating from occult sites becomes detectable, for example, in part because of the inherent application of the approximate inverse square law of radiation propagation. The procedure is known as radioimmunoguided surgery.
It is generally also thought that the spread of certain types of solid tumor cancers is caused by the migration (or draining) of tumor cells from the initial tumor to nearby lymph nodes and eventually to other vital sites via the lymphatic system. Cancer surgeons and medical oncologists believe the determination of whether a patient's primary tumor has spread to the lymph nodes is a major determinant of a patient's long-term prognosis. The spread of cancer to the patient's lymph nodes is established by the examination of the nodes by pathology to determine if tumor cells are present. If tumor cells are determined to be present in the lymph nodes, the patient's stage or severity of disease is increased. Surgeons perform procedures to identify the draining node(s) through the injection of a radioactive tracing agent at the site of the primary tumor. Following injection, the tracing agent follows the drainage path of the tumor to the nearest lymph node or nodes, referred to as the “sentinel node(s).” A gamma detection device is used to detect the path of the tracing agent. Since the lymph nodes are connected, oncologists believe that if the sentinel nodes show no sign of malignancy, then the downstream nodes in the pathway are likely to be clear of disease. As such, the removal of other nearby lymph nodes would be clinically unnecessary. Therefore, the ability to rapidly locate and biopsy sentinel nodes provides vital information to the physician in determining if the cancer has spread or if it is localized to the site of the primary tumor.
Recent technologies now allow the surgeon, via a combination of both isotopically labeled drugs and hand-held radiation detection devices, to provide enhanced surgical evaluation of tumor dissemination, e.g., removal of primary tumor-associated lymph nodes. Such surgical radiation detection instrumentation is comprised generally of a hand-held probe that is in electrical communication with a control console via a flexible cable or, more recently, via wireless communication. This control console is located within the operating room facility but out of the sterile field, while the hand-held probe and forward portions of its associated cable are located within that field. The hand-held radiation detecting probe is relatively small and performs in conjunction with a semiconductor detector such as cadmium zinc tellurium or a scintillating material such as or cesium iodide. Example instrumentation may be found in U.S. Pat. No. 4,782,840 and U.S. Pat. App. Pub. No. 2009/0326371, the disclosure of each of which is expressly incorporated by reference in its entirety herein.
A commercially available system and equipment to perform this radiation detection during surgery is the “Neoprobe Gamma Detection System”, available from Devicor Medical Products, Inc. Cincinnati, Ohio. See http://www.mammotome.com/neoprobe/.
Radioactive sources have been detected directly at whatever energy levels the source of radiation is producing by using detectors comprised of semiconductor (e.g., cadmium-zinc-tellurium) or scintillating (e.g., cesium iodide) materials. An output signal is produced when an incoming photon collides with material within the detector. The higher the energy level of the primary source of radiation, the more incoming photons can pass completely through the detector without colliding with any material, thus producing no output from the detector. For this reason, high energy detectors have necessarily been made of relatively “thick” (i.e., large cross-section volume) and dense materials to assure that a sufficient number of collisions occur to provide usable detector sensitivity. This characteristic of the detector is often referred to as “stopping power” or “absorption efficiency.”
In order to more efficiently detect high-energy radiation, it is usually necessary to increase the detector absorption by increasing the thickness of the detector crystal. Alternatively, a stacked crystal array having the absorption efficiency of a relatively thick monolithic crystal that may be biased with a relatively low voltage may be used. A stacked crystal array is described in U.S. Issued U.S. Pat. No. 8,269,185, “STACKED CRYSTAL ARRAY FOR DETECTION OF PHOTON EMISSIONS”, issued 18 Sep. 2012, which is hereby expressly incorporated by reference in its entirety herein.
U.S. Pat. No. 6,144,876, “SCANNING A RADIATION SOURCE WITH A COUNT RATE OUTPUT DERIVED WITH A DYNAMIC WINDOW ANALYSIS”, issued 7 Nov. 2000. This patent describes and claims a system in which count rate outputs of a probe-based radiation detection system are stabilized through the utilization of a dynamic window-based count analysis. Circular memory is utilized to record a sequence of segment count values. These values then are accessed and updated with respect to short scan intervals. The memory segments then are employed to develop a count sum over a count collection interval. That count sum is employed with algorithms adjusting the upper and lower edges of the dynamic window. A reported mean value, computed from the window upper edge or window lower edge, is utilized for creating a variable pitch output or for driving a bar graph. Background count and target count intervals are adjusted utilizing a data point predictive technique in combination with upper and lower time bounds.
U.S. Pat. No. 6,191,422, “RADIATION PROBE WITH COMPOUND SEMICONDUCTOR CRYSTAL PERFORMING IN A TRAPPING-DEPENDENT OPERATIONAL MODE” issued on 20 Feb. 2001. This patent describes and claims a hand-held radiation probe {which is configured} having a crystal thickness as well as a bias generated electrical field which have values to cause the semiconductor crystal to operate in a trapping-dependent operational mode wherein a trapping of substantially all carriers generated by radiation impinging upon the crystal forward face are trapped. The bias level voltage is selected to achieve adequate photopeak heights and to permit the windowing out of lower energy Compton scattering and other noise phenomena.
U.S. Pat. No. 6,218,669, “SURGICAL PROBE APPARATUS”, issued on 17 Apr. 2001. This patent describes and claims a surgical probe apparatus which incorporates a probe structure with a handle component and forward crystal mount wherein a cadmium-telluride crystal is rigidly mounted against movement. A cup-shaped window assembly is provided having an internal cylindrical tungsten shield which extends forwardly from the front face of the crystal to define an air gap as well as to support an aluminum window. The window assembly is threadably mounted upon the handle at a transition region forming an outwardly extending ramp. This ramp is used in conjunction with a polymeric retainer component with legs containing dog structures which hold a cylindrical tungsten collimator in biased position against the window when attached.
U.S. Pat. No. 6,259,095, “SYSTEM AND APPARATUS FOR DETECTING AND LOCATING SOURCES OF RADIATION” issued on 10 Jul. 2001. This patent describes and claims a system and apparatus for locating sources of radiation emanating from predetermined radionuclides. The apparatus incorporates a large window display utilizing icon imagery to identify counting functions such as target count and background. A variety of radionuclide modes of operation can be selected by the operator and the system automatically defaults to detector bias selection and window reference voltage selection in correspondence with the elected radionuclide. A bar graph readout apprises the user of the amount of time or count level remaining in a target or background procedure and the flashing of icon identifiers occurs during such procedures. Pulse validation is improved by the utilization of a discriminator which evaluates pulse width.
U.S. Pat. No. 6,272,373, “SCANNING SYSTEM AND METHOD FOR LOCATING SOURCES OF RADIATION EMISSION”, issued 7 Aug. 2001. This patent describes and claims a scanning system for a hand-held probe employing a 50 ms scanning interval in conjunction with circular memory. Combinations of segment bins from the circular memory are acquired following each short scanning interval. A threshold is computed for each combination initially based upon a threshold factor which is statistically significant and has a value of three. Audible cueing is developed if any three of six of these combinations of segment bin scan counts exceeds a correspondingly computed threshold value. Thereafter, the threshold factor is diminished to a value of one and the same thresholding tests are carried out to maintain audible cueing. Running count rates are computed as the average of the entire circular buffer memory divided by its corresponding total collection time. This computation is provided on a one half second updated basis.
All of the above issued US Patents are expressly incorporated by reference in their entirety herein.
The above-described systems can be burdensome because the entire probe unit (including detector and handle), must be sterilized between every use. Furthermore, the entire probe unit must be replaced or sent for repair if a malfunction occurs in any part. Thus, there is a need in the art for a probe that avoids these problems.